Polio is an infectious disease caused by a poliovirus. Polioviruses infect human by an oral route, proliferate in the intestinal tract, and enter the central nervous system through the blood. The proliferation within large motor neutrons of polioviruses that have entered the central nervous system causes neuronal degeneration and necrosis, triggering acute flaccid paralysis in the limbs. Moreover, when the poliovirus affects the medullary respiratory center, death from respiratory paralysis may result. Polio vaccines are widely used to suppress the onset of polio which triggers such severe symptoms.
Two types of polio vaccines are used: oral live polio vaccines and inactivated polio vaccines. Oral live polio vaccines are vaccines which use attenuated strains of poliovirus (Sabin strains). Attenuated strains of poliovirus that administered orally cause normal infections. Polioviruses from oral live polio vaccines grow well in the intestines, resulting in the formation of localized immunity within the intestines. In addition, when polioviruses from an oral live polio vaccine enter the blood and cause viremia, this also stimulates the production of antibodies within the blood. However, because the ability of attenuated strains of polioviruses to proliferate within the central nervous system is very weak, they generally do not cause paralysis. In the body of the inoculee, polioviruses from the oral live polio vaccine multiply and are excreted in the stools about 4 to 6 weeks following inoculation. The excreted viruses will infect people around the inoculee who have a weak immunity or no immunity to polio, conferring immunity or exhibiting a potentiating effect in the same way as in the inoculee.
However, in the course of repeated growth within the body of the inoculee or in the course of repeated growth in the body of a person infected by excreted viruses, an attenuated strain of poliovirus from an oral live polio vaccine sometimes gives rise to mutations in a highly virulent direction. In very rare instances, such mutants cause vaccine-associated paralysis.
An inactivated polio vaccine is a vaccine which has lost its infectiousness by inactivation of the poliovirus with formalin. Because an inactivated polio vaccine neither multiplies within the body of the inoculee nor infects people around the inoculee, it will not cause vaccine-associated paralysis. Highly virulent strains have hitherto been used to prepare inactivated polio vaccines, but advances have also been made recently in the development of attenuated strains (Sabin strains) (Biologicals 34, 151-154 (2006); Dev. Bil. Basel. Karger 105, 163-169 (2001), Clinical Virology 30, No. 5, 336-343 (December 2002)). The somewhat poorer growth of attenuated strains (Sabin strains) than highly virulent strains has been regarded as a drawback.
Vaccines which contain a Bordetella pertussis protective antigen, a diphtheria toxoid and a tetanus toxoid are widely used as diphtheria-tetanus-pertussis combined vaccines.
Polyvalent vaccines composed of an acellular pertussis vaccine, a diphtheria toxoid, a tetanus toxoid and inactivated poliovirus are known (Published Japanese Translation of a PCT Application No. 2000-504032).
Vero cells are passage cells from the kidneys of green monkeys. Because these cells have a broad sensitivity to various types of viruses, they are widely used in virus cultivation. A method for preparing an enterovirus type 71 vaccine that been reported in the literature includes culturing Vero cells on a microcarrier and using the cultured Vero cells to grow enterovirus 71 (“Optimization of microcarrier cell culture process for the inactivated enterovirus type 71 vaccine development,” by Suh-Chin Wu, et al.: Vaccine 22, 3858-3864 (2004)). General cell culturing conditions using a microcarrier have also been described (Microcarrier cell culture principles & methods: Pharmacia LKB, Biotechnology, 1988).